Is AMBP p.Ser51Phe (c.152C>T) pathogenic?

AMBP p.Ser51Phe (c.152C>T) is classified Uncertain significance in AMBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely pathogenic (0.9504); Rare (popmax 0.117%, sas).

How common is AMBP p.Ser51Phe (c.152C>T) in the general population?

AMBP p.Ser51Phe (c.152C>T) is rare (popmax 0.117%, sas) (gnomAD).

What do computational predictors say about AMBP p.Ser51Phe (c.152C>T)?

AlphaMissense predicts likely pathogenic (score 0.9504) — an in-silico prediction, not a clinical call.

AMBP p.Ser51Phe

c.152C>T · rs143305185 · VCV2456983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9504 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.117%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9504	likely pathogenic · top 8% in AMBP
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -14.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 4,101 bp · p 0.37 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.117% South Asian · 107/91,070 alleles

Filtering AF 0.0994% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0927%

Overall 0.0126% 203/1,614,016 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.117%	851
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
Middle Eastern	0.066%	1,515
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.0117%	8,572
East Asian	0.00446%	22,437
European (non-Finnish)	0.00415%	24,081
African / African-American	0.00133%	74,982

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AMBP
Protein: p.Ser51Phe
Coding: c.152C>T
MANE Select: NM_001633
dbSNP: rs143305185
Type: single nucleotide variant
Location: chr9:114076706 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 11 PDB
Residue 51: a β-strand

Full AMBP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMBP p.Ala13Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala19Val Uncertain significance ★ ⚠ same type
AMBP p.Ala255Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala285Val Uncertain significance ★ ⚠ same type
AMBP p.Ala304Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala48Thr Uncertain significance ★ ⚠ same type
AMBP p.Ala74Thr Uncertain significance ★ ⚠ same type
AMBP p.Arg185Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ambp-p-ser51phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown